CALCITONIN-GENE-RELATED PEPTIDE AFFORDS GASTRIC-MUCOSAL PROTECTION BYACTIVATING POTASSIUM CHANNEL IN WISTAR RAT

Background & Aims: Calcitonin gene-related peptide (CGRP) protects the gastric mucosa against injurious stimuli in various experimental mode ls. The underlying mechanism could be the increase in gastric mucosal blood flow (GMBF), A number of endogenous vasodilators exert their eff ects through the activation of adenosine triphosphate (ATP)-sensitive potassium (K-ATP) channels on vascular smooth muscle, The present expe riments were performed to elucidate whether CGRP increases GMBF throug h the activation of K-ATP channels and whether the channels are involv ed in the protection by CGRP of gastric mucosa, Methods: GMBF was dete rmined by the hydrogen-clearance technique in male Wistar rats, Mucosa l lesions were produced by intragastric superfusion with 0.15N HCl and 15% ethanol for 40 minutes, Effects of an agonist (Y-26763, intra-art erially) and an inhibitor (glibenclamide, intravenously) of K-ATP chan nels were tested, Results: Y-26763 increased GMBF, which was abolished by glibenclamide, and a CGRP-induced increase in GMBF was attenuated by glibenclamide. Macroscopic and microscopic lesions were exacerbated by human CGRP-(8-37) (a CGRP-1 receptor antagonist; intra-arterially) and glibenclamide but were ameliorated by exogenous CGRP (intra-arter ially). Conclusions: CGRP protects the gastric mucosa against ulceroge nic stimuli, at least in part, through the activation of K-ATP channel s in rats.